Cohort profile update: Tehran cardiometabolic genetic study.

The Tehran cardiometabolic genetic study (TCGS) is a large population-based cohort study that conducts periodic follow-ups. TCGS has created a comprehensive database comprising 20,367 participants born between 1911 and 2015 selected from four main ongoing studies in a family-based longitudinal framework. The study's primary goal is to identify the potential targets for prevention and intervention for non-communicable diseases that may develop in mid-life and late life. TCGS cohort focuses on cardiovascular, endocrine, metabolic abnormalities, cancers, and some inherited diseases. Since 2017, the TCGS cohort has augmented by encoding all health-related complications, including hospitalization outcomes and self-reports according to ICD11 coding, and verifying consanguineous marriage using genetic markers. This research provides an update on the rationale and design of the study, summarizes its findings, and outlines the objectives for precision medicine.

Anti-cancer impact of Hypericin in B-CPAP cells: Extrinsic caspase dependent apoptosis induction and metastasis obstruction.

Thyroid cancer is the most common type of endocrine-related cancer. According to the literature, its incidence is not very high, but its rate increasing especially in developed countries. With this regard, finding approaches to prevent, and exert anti-tumor activity with the least side effects on the normal cells at the next step after diagnosis is demanded. Herbal medicine is a branch of integrative oncology that seems to be a practically beneficial goddess for cancer treatment in many cases. Here we utilized Hypericin (HYP) to investigate its anti-tumor (apoptotic and anti-metastatic) activity on B-CPAP (a thyroid cancer cell line) and cytotoxicity on TPC-1 (thyroid cancer cell line with wild type TP53) cell lines. To assess whether HYP may exert preventive and anti-tumor effects and does not have a potential side effect, we dubbed the experiments on the fibroblast cells (as a normal cell line). Cytotoxicity and kind of cellular death were examined by MTT and AnnexinV/PI respectively. Extrinsic/intrinsic apoptosis pathway induction was clarified by western blotting on pro/cleaved caspases 9, 8, and 3. According to our data HYP induces an extrinsic apoptosis pathway and no other types (necroptosis, necrosis, etc.) in B-CPAP cells. Moreover, CDH1 mRNA expression calculated to be up-regulated, and that of LGALS3 down-regulated in the B-CPAP cell line after treatment. Besides tumor cytotoxic activity, we suggest that HYP impedes with invasion and/or metastasis process.

The Relationship Between Coronary Artery Disease and Genetic Polymorphisms of Melanoma Inhibitory Activity 3.

BACKGROUND: Melanoma Inhibitory Activity 3 regulates the plasma level of LDL cholesterol. The c.3169 + 315G > A single-nucleotide polymorphism of the MIA3 gene has been reported to be associated with serum coronary artery disease (CAD). However, there have been no studies analyzing the association of this polymorphism with CAD in Iranian individuals with CAD. OBJECTIVES: Therefore, in the present study we have investigated the potential protective effect of the rs3008621 MIA3 polymorphism in 188 subjects with and without CAD. MATERIALS AND METHODS: Genotyping of the MIA3 gene was undertaken using TaqMan real-time PCR in all subjects. Anthropometric and biochemical features, including HDL, LDL, and TG were assessed in all subjects. RESULTS: The CAD patients had significantly (P < 0.05) higher BMI and significantly higher levels of TG, LDL, SBP, and DBP, while the level of HDL was lower compared to that of the control group. the MIA3 gene polymorphism was not associated with CAD in our population sample. CONCLUSIONS: The MIA3 polymorphism is unlikely to play an important role in CAD in the Iranian population. However, further studies are needed in a larger population to confirm this.

Analysis of rs6725887 in the WD Repeat Protein 12 in Association with Coronary Artery Disease in Iranian Patients.

Although genetic variants that affect susceptibility to coronary artery disease (CAD) have been greatly known, a number of these single nucleotide polymorphisms (SNPs) remain to be analyzed in populations with different ethnicities. CAD is influenced by numerous genetic, environmental, and lifestyle factors, and is an important reason for mortality around the globe. In this study, a novel SNP (rs6725887) in the WD Repeat Protein 12 (WDR12) gene was selected to be examined in Iranian patients with CAD. Ninety eigth healthy controls and one hundred and one CAD patients were enrolled from Iranian population, and their clinical data were collected for further comparisons. After DNA extraction from each sample, genotypes were characterized by Taq Man probe real- time PCR assay. Statistical analyses were performed to evaluate genotype and allele frequencies and compared the values with clinical variables. Body mass index, blood pressure, fasting blood sugar, LDL, HDL, cholesterol, and triglyceride significantly differed in CAD and control groups. Genotype and allele frequencies of rs6725887 in CAD patients and controls showed no significant association in the distribution. However, clinical parameters of CAD patients like HDL, LDL, FBS, TG, DBP and SBP had significantly (P<0.05) higher levels compared to control group. The rs6725887 polymorphism is unlikely to play a key role in CAD risk in our population. Further additional samples are required for better appreciation of the influence of WDR12 SNP on CAD occurrence.

Association Study of rs3184504 C>T Polymorphism in Patients With Coronary Artery Disease.

Cardiovascular disease has become the main factor of death and birth defects in the world and also in Iran. New clinical studies have shown that early diagnosis of patients with coronary artery disease (CAD) can contribute to effective prevention or therapeutic structures, which reduce mortality or the next chance of cardiovascular events, and increase the quality of life. Most studies on CAD disease and its genetic risk factors so far, have been done excluding the Iranian population. PubMed was used to search for all relevant studies published on or before 2013 and rs3184504 was selected for association study for CAD. A total of 200 subjects with 100 cases and 100 controls were ultimately included in the analysis. Blood samples were collected and after DNA extraction the DNA analysis was performed by TaqMan Probe Real Time PCR to evaluate the association between candidate variant with the disease and some blood biochemical factors. Our study demonstrated that there was not a direct association between rs3184504 C>T variant with risk of CAD in Iranian population, whereas, there is a significant association between this variant with increased blood LDL and diastolic blood pressure. Further molecular analysis and other disease association studies are necessary in the Iranian population.

Development and Validation of a Reversed-phase HPLC Method for Assay of the Decapeptide Cetrorelix Acetate in Bulk and Pharmaceutical Dosage Forms.

A gradient reversed-phase high performance liquid chromatography (HPLC) method was developed for the assay of cetrorelix acetate, a synthetic decapeptide with gonadotropin-releasing hormone (GnRH) antagonistic activity used in infertility treatment. The HPLC method, which is used to determine cetrorelix in bulk and pharmaceutical dosage forms, was validated per ICH guidelines. The chromatographic separation was achieved on a C18 reversed-phase column using acetonitrile, water and trifluoroacetic acid (TFA) as mobile phase and wavelength was set at 275 nm. The calibration curve was linear (r2 = 0.999) over cetrorelix concentrations ranging from 62.50 to 12.50 µg/mL (n = 6). The limits of detection (LOD) and quantification (LOQ) were calculated from the peak-to-noise ratio as 15.6 and 62.5 µg/mL, respectively. The method had an accuracy of > 97% and intra- and inter-day RSD of < 0.3% and < 1.6%, respectively and was validated with excellent specificity, sensitivity, and stability. The validated method was successfully applied for determination of cetrorelix in bulk and pharmaceutical dosage forms.